中国临床心理学杂志

睡眠剥夺对抑郁模型大鼠海马CREB表达的影响

作者：赵小赋¹ 王玉锋² 朱金富²

单位：1. 解放军第91中心医院全军精神疾病防治中心河南焦作 454003
2. 新乡医学院心理学系河南新乡 453003

分类号：R395.1

出版年,卷(期):页码：2012,20(4):461-464

摘要：

目的:探讨睡眠剥夺通过影响海马区CREB含量及活性而产生的快速抗抑郁机制。方法:将40只SD大鼠随机分为正常对照组、抑郁模型组、睡眠剥夺组和水环境对照组。用改良多平台睡眠剥夺法(MMPM)对用慢性不可预见性应激抑郁模型方法建立的抑郁大鼠模型进行睡眠剥夺。用旷场实验和强迫游泳实验测试其行为变化,以及用免疫组化法测试海马CREB、P-CREB的含量。结果:①睡眠剥夺组大鼠与抑郁模型组相比旷场实验的水平得分与垂直得分均明显升高,潜伏期明显缩短。②海马CA1、CA3、DG区的CREB及p-CREB平均光密度值比较中,抑郁模型组均显著低于正常对照组,睡眠剥夺组均显著高于抑郁模型组。结论:睡眠剥夺可明显改善抑郁大鼠的抑郁样行为;海马部位CREB含量及活性的增高可能参与了睡眠剥夺的快速抗抑郁作用。

Objective: To explore the changes of CREB levels and activities in hippocampus resulting from sleep deprivation,and then to reveal the mechanism for rapid antidepressant aroused by sleep deprivation. Methods: 40 SD rats were randomly divided into normal control group, chronic stress group, sleep deprivation group and tank contral group. 10 rats in each group. The depression animal model was established by chronic mild unpredictable stress methods. Sleep deprivation was preformed by the modified multiple platform method (MMPM). The animal model and the effect of antidepressant were evaluated by the Open Field test and Forced Swimming test. The expression levels of CREB and P-CREB were separately observed by immunohistochemical technology in hippocampus CA1, CA3 and DG. Results: ①In the CUMS depressant animal model, compared with the normal control rats, following 72-hour sleep deprivation, ambulation and rearing increased, and the latent period in the center decreased. ②CREB and P-CREB: The average values of optical density(OD) in hippocampus CA1, CA3, DG of the model group was lower than that of the normal control group significantly, and that of the sleep deprivation group was higher than that of the model group. Conclusion: Rats showed depressive behaviors after 21 days stresses, while 72 hours sleep deprivation could reverse this effect. The up regulation of the expression and phosphorylation of CREB by sleep deprivation may participate in the antidepressant-like effect of sleep deprivation.

基金项目：

河南省科技发展计划项目(102102310069);新乡医学院重点领域项目(ZD2011-29)

作者简介：

参考文献：

[1] Bunney JN,Potkin SG. Circadian abnormalities,molecular Clock genes and chronobiological treatments in depression[J].British Medical Bulletin,2008,(01):23-32.
[2] Benedetti F,Barbini B,Colombo C,Smeraldi E. Chronotherapoutics in a psychiatric ward[J].Sleep Medicine Reviews,2007.509-522.
[3] Yamada S,Yamamoto M,Ozawa H. Reduced phosphorylation of cycli cAMP-responsive elementbinding protein in the postmortem orbitofrontal cortex of patients with major depressive disorder[J].Journal of Neural Transmission,2003,(06):671-680.doi:10.1007/s00702-002-0810-8.
[4] Yuan P,ZhouR,WangY. Altered levels ofextracellular signal regulated kinase signaling proteins in postmortem frontal cortex of individualswithmood disorders schizophrenia[J].Journal of Affective Disorders,2010,(1-2):164-169.
[5] Tanya LW,Kathryn ES,Rachael LN. Effects of cyclic adenosine monophosphate response element binding protein overexpression in the basolateral amygdala on behavioral models of depression and anxiety[J].Society of Biological Psychiatry,2004,(03):151-160.
[6] Berger M,Vollmann J,Hohagen F. Sleep deprivation combined with consecutive sleep phase advance as a fastacting therapy in depression:An open pilot trial in medicated and unmedicated patients[J].American Journal of Psychology,1997,(06):870-872.

[7] Willner P. Validity,reliability and utlity of the chronic mild stress model of depression:A 10-year review and evaluation[J].Psychopharmacology,1997.319-329.
[8] 黄建欧,赵忠新. 大鼠睡眠剥夺方法的研究进展[J].中华神经医学杂志,2004,(03):229-231.doi:10.3760/cma.j.issn.1671-8925.2004.03.029.
[9] 朱宇章,彭淼,丁宝坤. 慢性应激对大鼠外显行为及海马亚区脑源性神经营养因子表达差异性的影响[J].中国行为医学科学,2004.481-483.
[10] 李晶晶,袁勇贵,侯钢. 不同剂量文拉法辛对抑郁模型大鼠海马区pCREB和BDNF表达的影响[J].中国神经精神疾病杂志,2008,(11):645-649.doi:10.3969/j.issn.1002-0152.2008.11.002.
[11] 许志强,高长越,方传勤. 睡眠剥夺对小鼠学习记忆和海马pCREB水平的影响[J].中华行为医学与脑科学杂志,2010,(05):392-393.doi:10.3760/cma.j.issn.1674-6554.2010.05.003.
[12] 宋炜熙,胡随瑜,王哲. 白松片对抑郁模型大鼠海马DAT mRNA表达的影响[J].中国临床心理学杂志,2006,(05):547-549,541.doi:10.3969/j.issn.1005-3611.2006.05.040.
[13] 杨国愉,皇甫恩,张大均. 人参皂甙对睡眠剥夺大鼠学习记忆和活动性的影响[J].中国临床心理学杂志,2007,(01):81-84.doi:10.3969/j.issn.1005-3611.2007.01.031.
[14] Xu Y,Ku B,Tie L. Curcumin revemes the effects of chronic stress on behavior,theHPA axis,BDNF expression and phosphorylation of CREB[J].Brain Research,2006,(01):56-64.doi:10.1016/j.brainres.2006.09.009.
[15] Li H,Zhang L,Huang Q. Differential expression of mitogen-activated protein kinase signaling pathway in the hippocampus of rats exposed to chronic unpredictable stress[J].Behavioural Brain Research,2009,(01):32-37.doi:10.1016/j.bbr.2009.06.036.
[16] 郑晖,马光瑜,徐小虎. 应激对大鼠海马CREB、ERK活性的影响[J].中国行为医学科学,2007.103-105.
[17] Jayatissa MN,Bisgaard CF,West MJ. The number of granule cells in rat hippocampus is reduced after chronic mild stress and re-established after chronic escitalopram treatment[J].Neuropharmacology,2008,(03):530-541.doi:10.1016/j.neuropharm.2007.11.009.
[18] McLaughlin KJ,Gomez JLB. The effects of chronic stress on hippocampal morphology and function:an evaluation of chronic restraint paradigms[J].Brain Research,2007.556-564.

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